58 diabetes insipidus
gold standard, not only in making the diagnosis of
osteoporosis but also in following the patient’s
response to therapy for the treatment of osteo-
porosis.
diabetes insipidus (DI) A rare metabolic/endocrine
disorder characterized by massive losses of body flu-
ids through urination. The antidiuretic hormone
(ADH), also known as vasopressin, which is made
by the hypothalamus and stored in the pituitary
gland, is at a reduced level among patients with DI.
In a healthy person, ADH works to decrease urine
flow by increasing the reabsorption of salt and
water in the kidney tubules.
Diabetes insipidus has no relationship to DIA-
BETES MELLITUS, although the twin symptoms of fre-
quent urination and extreme thirst are common to
both diseases. Diabetes insipidus may occur abrupt-
ly in individuals of any age, although it is more
common among adults.
Types and Causes of Diabetes Insipidus
DI is caused by damage to the pituitary gland,
which may result from a head injury, an infection,
a tumor, or a variety of other causes. Some experts
believe DI may be a form of autoimmune disorder.
Diabetes insipidus may also be an inherited disease.
Hereditary forms of DI are called familial diabetes
insipidus or familial neurohypophysial diabetes
insipidus.
Central DI is the most common form of diabetes
insipidus. Unless otherwise stated, researchers who
are discussing diabetes insipidus are referring to
central DI. Another form of DI is nephrogenic DI,
caused by a disorder of the kidneys in which they
are unable to respond to the ADH that is produced.
Nephrogenic DI may sometimes be caused by med-
ications such as lithium.
Dipsogenic DI, a rare form of diabetes insipidus, is
caused by a disorder in the hypothalamus that affects
the mechanism causing thirst. In rare cases, pregnant
women may develop gestational diabetes insipidus,
which is caused by an enzyme in the placenta.
Signs and Symptoms of Diabetes Insipidus
Whether the illness is inherited or acquired, the
symptoms of diabetes insipidus include frequent
urination (typically, greater than four liters per day,
with very dilute urine), fatigue, and excessive thirst.
Unless the person with diabetes insipidus drinks
copious quantities of fluid, he or she will become
severely dehydrated and constipated. However, the
patient will not have hyperglycemia (high levels of
blood glucose), which is the hallmark feature of
both Type 1 and Type 2 diabetes. Some patients
with DI also have severe night sweats.
Infants and Children with DI
If infants with the disease are not treated quickly,
they may suffer from irreversible brain damage or
developmental problems, such as mental retarda-
tion and physical delays. Symptoms of diabetes
insipidus in a baby are fever, vomiting, and con-
vulsions, with high levels of sodium found in the
blood upon laboratory examination. Infants and
children with diabetes insipidus may also have
FAILURE TO THRIVE and experience growth deficits.
Researchers studied 79 children with diabetes
insipidus and reported on their findings in the New
England Journal of Medicine. The children had a
median age of seven years. The researchers per-
formed MAGNETIC RESONANCE IMAGING (MRI) scans
on the children, and they found that most of the
children had certain abnormalities. For example,
18 of the patients had an intracranial tumor, two
had skull fractures, and 12 of the children had
Langerhans’ cells histiocytosis.
Many of the children (61 percent) showed ante-
rior pituitary deficiencies, particularly of growth
hormone, within about a year from the onset of
their diabetes insipidus.
In about 25 percent of the children, there
appeared to be a link between contracting a virus
and the subsequent onset of diabetes insipidus. In
about 30–50 percent of the cases, the cause for the
diabetes insipidus was unknown.
Adults and DI
Among adults, diabetes insipidus is commonly
caused by pituitary tumors of many types as well as
by the surgery and/or radiation used to treat them.
Typically these tumors are benign. However, they
damage the pituitary gland by their mass effect, as
there is very little extra room in the sella turcica
where the pituitary gland sits. Malignant tumors

may also metastasize to the pituitary gland and
cause DI.
A significant head trauma, such as that which
can be caused by motor vehicle accidents or by
gunshot wounds, can also cause DI to occur.
Granulomatous diseases may also cause DI. These
diseases cause the body to respond by creating
granulomas, which are large cells derived from
white blood cell monocytes and used as part of the
body’s immune system defense.
Anything that damages the hypothalamus,
which sits directly adjacent to the pituitary gland,
may also lead to DI. This occurs because the hypo-
thalamus is where ADH is made prior to its transit
to the pituitary gland.
Diagnosis and Treatment
The diagnosis of diabetes insipidus is based on the
patient’s symptoms and on blood tests of glucose
levels that rule out a diagnosis of either Type 1 or
Type 2 diabetes. In order to diagnose DI, the
endocrinologist must document that the patient is
producing a large flow of urine that is quite dilute
and that fails to concentrate to the appropriate
stimuli. In healthy people, if they do not drink
water over a period of time, appropriate hormonal
changes will ensue that cause the urine to become
more concentrated and thus they will lose less
water in their urine and their lives will be sus-
tained. However, in contrast, when individuals
with DI fail to drink water, the hormonal changes
do not occur and instead, the body continues to
pour out diluted urine. As a result, the water dep-
rivation test is used to diagnose DI.
To determine the presence of diabetes insipidus,
a fluid deprivation test is needed on occasion, espe-
cially if the ADH deficiency is only partial.
Sometimes a test known as a dehydration test is
used. This test is used especially if the ADH defi-
ciency is partial or if there is a suspicion of the pres-
ence of psychogenic polydipsia, which is an
extreme intake of water that may stem from an
emotional or psychotic disorder such as untreated
schizophrenia.
Diabetes insipidus is usually treated with desmo-
pressin acetate (DDAVP), a hormone that is avail-
able in several forms: an intravenous or
subcutaneous preparation, a nasal spray, a liquid,
diabetes insipidus 59
or a tablet. Physicians must be careful to prescribe
the correct dose of this medication. If excessive
amounts of DDAVP are administered, patients may
become water intoxicated. Patients taking this drug
must also be reassessed several times per year.
Other drugs besides DDAVP that increase ADH
secretion are generally not very effective and, con-
sequently, are rarely used. However, in a study
reported in a 1999 issue of the Archives of Internal
Medicine, researchers treated 20 patients with cen-
tral diabetes insipidus with indapamide (Lozol), an
antihypertensive diuretic. The drug worked well on
most patients.
In the case of nephrogenic diabetes insipidus,
recommendations of low-salt diets, thiazide diuret-
ics, and nonsteroidal anti-inflammatory drugs
(NSAIDs) are often used for patients. Gestational
DI usually resolves when the pregnancy ends.
For further information, contact the following
organizations:
Diabetes Insipidus Foundation, Inc.
4533 Ridge Drive
Baltimore, MD 21229
(410) 247-3953
National Kidney and Urologic Diseases
Information Clearinghouse
3 Information Way
Bethesda, MD 20892
(800) 891-5390 (toll-free)
Nephrogenic Diabetes Insipidus Foundation
P.O. Box 1390
Eastsound, WA 98245
(888) 376-6343 (toll-free)
http://www.ndif.org
Maghnie, Mohamad, M.D., et al. “Central Diabetes
Insipidus in Children and Young Adults.” New England
Journal of Medicine 343, no. 14 (October 5, 2000):
998–1,007.
Petit, William A. Jr., M.D., and Christine Adamec. The
Encyclopedia of Diabetes. New York: Facts On File, Inc.,
2002.
Tetiker, Tamer, M.D., Murat Sert, M.D., and Mustafa
Kocak, M.D. “Efficacy of Indapamide in Central
Diabetes Insipidus.” Archives of Internal Medicine 159,
no. 17 (1999): 2,085–2,087.
60 diabetes mellitus
diabetes mellitus (DM) Common name for both
Type 1 and Type 2 diabetes. Diabetes mellitus is a
complex disorder of carbohydrates, proteins, and
fats that leads to premature death, usually due to
heart attack and stroke. Many experts think that
although diabetes is commonly considered a dis-
ease of sugar, it is more accurately a vascular dis-
ease that severely affects blood vessels throughout
the body.
Type 1 diabetes is an autoimmune disorder in
which all the insulin-producing beta cells in the
pancreas are destroyed, with patients dependent
upon taking insulin to live. With Type 2 diabetes,
patients’ bodies do make insulin but have resistance
to its effects. They are unable to make adequate
insulin to control their glucose levels and the result-
ing metabolic disarray. Most patients with Type 2
diabetes can be treated with nutrition, exercise, and
oral medications. About 7 percent of patients with
Type 2 diabetes lose the ability to make insulin and,
consequently, require insulin therapy.
Risk Factors
According to the Centers for Disease Control and
Prevention (CDC), as of this writing about 18 mil-
lion people in the United States, or 6.3 percent of
the population, have diabetes. This number
includes about 6 million people who have the dis-
ease but do not realize it. From 90–95 percent of all
patients with diabetes mellitus have Type 2 dia-
betes, while 5–10 percent have Type 1 diabetes,
requiring insulin injections. These figures do not
include women with gestational diabetes, which
refers to an estimated 135,000 pregnant women in
the United States who did not have diabetes prior
to their pregnancies.
About one in every five adults over age 65 has
diabetes. The National Diabetes Information
Clearinghouse estimated that the direct medical
costs of diabetes mellitus were $92 billion in 2002.
There are racial differences among patients with
diabetes. African Americans and Native Americans/
Alaska Natives have a greater risk for developing
Type 2 diabetes than Caucasians. In contrast,
Caucasians are more likely to be diagnosed with
Type 1 diabetes.
Most people with diabetes are diagnosed in
adulthood. According to the CDC, only 7.2 percent
of adults with diabetes were diagnosed between
birth and age 19 years (see Table I).
The percentages of people in the United States
who have been diagnosed with diabetes also varies
greatly from state to state according to surveillance
data for 2001 from the CDC. The greatest percent-
ages were found in Puerto Rico (9.8 percent),
Alabama (9.6 percent), and Guam (9.5 percent).
The lowest percentages were found in Alaska (4.0
percent), Utah (4.2 percent), and Minnesota (4.4
percent) (see Table II).
TABLE I: DISTRIBUTION OF AGE AT DIAGNOSIS
OF DIABETES AMONG ADULTS AGED 18–79 YEARS,
UNITED STATES, 2000
Age in Years Percent
0–9 2.4
10–19 4.8
20–29 6.6
30–39 14.4
40–49 24.2
50–59 24.8
60–69 17.0
70–79 5.7
Source: Diabetes Surveillance System, National Center for Chronic
Disease Prevention and Health Promotion, Centers for Disease
Control and Prevention.
Risks Are Increasing for Developing Diabetes
The risk of developing diabetes mellitus is rising.
For example, according to an article in a 2003 issue
of the Journal of the American Medical Association,
researchers estimated the lifetime risk of develop-
ing diabetes among children born in 2000. They
estimated that the risk was 32.8 percent for males
and 38.5 percent for females.
Hispanics had the highest potential risks for
developing diabetes, or 45.4 percent for males and
52.5 percent for females. Said the researchers, “The
lifetime risk of diabetes is comparable with or high-
er than that for many diseases and conditions that
are perceived as common. For example, the life-
time risk of diabetes is considerably higher than the
 diabetes mellitus 61

TABLE II: PREVALENCE OF ADULTS WHO REPORTED EVER HAVING BEEN TOLD BY A
HEALTH PROFESSIONAL THAT THEY HAD DIABETES, 1991, 2000, AND 2001, AND BY SEX, 2001—
UNITED STATES, BEHAVIORAL RISK FACTOR SURVEILLANCE SYSTEM

Both sexes Men Women

(%)
2001 2000 1991 Difference (2001) (2001)

State or Territory % 95% CI* (±) % 95% CI (±) % 95% CI (±) 1991–2001 % 95% CI (±) % 95% CI (±)

Alabama 9.6 1.2 7.4 1.2 5.1 1.0 89.3 10.5 2.0 8.8 1.4
Alaska 4.0 1.0 3.8 1.4 4.3 1.3 –7.8 4.0 1.4 4.0 1.4
Arizona 6.1 1.0 5.9 2.2 3.8 1.0 60.1 7.3 1.8 4.9 1.2
Arkansas 7.8 1.2 6.2 1.0 4.8 1.2 63.9 8.4 1.8 7.2 1.4
California 6.5 1.0 6.8 1.2 4.8 0.9 36.8 5.8 1.2 7.1 1.4
Colorado 4.6 1.0 5.1 1.2 2.9 0.8 56.5 5.6 1.8 3.7 1.2
Connecticut 6.3 0.6 5.5 0.8 4.6 1.1 37.6 6.5 1.0 6.0 0.8
Delaware 7.1 1.0 6.4 1.2 4.9 1.2 43.7 7.5 1.8 6.7 1.4
District of Columbia 8.3 1.6 7.2 1.4 6.7 1.7 24.3 9.6 2.5 7.2 1.8
Florida 8.2 1.0 6.9 0.8 5.1 1.0 60.5 9.1 1.6 7.3 1.2
Georgia 6.9 0.8 6.8 1.0 5.6 1.2 23.2 6.5 1.4 7.2 1.2
Hawaii 6.2 1.2 5.2 0.8 6.5 1.2 –4.0 6.8 2.0 5.6 1.2
Idaho 5.4 0.8 4.9 0.8 3.7 0.9 45.2 5.2 1.0 5.7 1.0
Illinois 6.6 0.8 6.2 1.0 5.1 1.0 30.2 6.7 1.4 6.6 1.2
Indiana 6.5 0.8 6.0 1.0 5.4 1.0 20.8 6.3 1.2 6.8 1.0
Iowa 5.7 0.8 6.1 1.0 3.8 1.0 51.6 5.8 1.2 5.6 1.0
Kansas 5.8 0.8 5.9 0.8 -† — — 5.5 1.0 6.1 1.0
Kentucky 6.7 0.8 6.5 0.8 4.8 1.0 40.8 6.9 1.2 6.4 0.8
Louisiana 7.6 0.8 6.6 0.8 6.3 1.3 20.3 6.9 1.2 8.2 1.0
Maine 6.7 1.2 6.0 1.2 4.2 1.2 60.3 7.0 2.0 6.5 1.4
Maryland 6.9 1.0 6.4 1.0 5.2 1.2 32.7 7.1 1.6 6.6 1.4
Massachusetts 5.6 0.6 5.8 0.6 4.4 1.3 26.7 6.0 1.0 5.2 0.8
Michigan 7.2 1.0 7.0 1.0 5.4 0.9 34.3 6.8 1.4 7.6 1.2
Minnesota 4.4 0.6 4.9 1.0 3.7 0.7 18.3 4.4 1.0 4.3 1.0
Mississippi 9.3 1.2 7.6 1.2 7.0 1.4 32.1 8.8 2.0 9.7 1.4
Missouri 6.6 1.0 6.7 1.0 4.1 1.0 63.0 7.0 1.6 6.2 1.2
Montana 5.6 1.0 4.9 1.0 4.9 1.3 13.4 4.9 1.2 6.2 1.6
Nebraska 5.2 0.8 4.9 1.0 4.8 1.2 8.3 4.9 1.2 5.5 1.0
Nevada 5.7 1.4 6.8 2.0 — — — 5.2 1.4 6.2 2.2
New Hampshire 5.4 0.8 4.4 1.0 4.7 1.2 14.2 5.8 1.2 5.0 1.0
New Jersey 7.1 1.0 5.8 0.8 4.3 1.1 64.0 7.3 1.4 7.0 1.2
New Mexico 6.2 1.0 6.5 1.0 3.4 1.1 80.2 5.9 1.4 6.5 1.2
New York 6.6 1.0 6.3 1.0 5.2 1.1 27.7 6.4 1.4 6.8 1.4
North Carolina 6.7 1.0 6.4 1.0 6.3 1.2 6.2 6.8 1.4 6.7 1.0
North Dakota 5.1 1.0 5.2 1.2 4.4 1.0 16.4 4.7 1.4 5.6 1.2
Ohio 7.2 1.0 6.4 1.2 4.5 1.4 61.8 7.5 1.6 6.9 1.2
Oklahoma 7.7 1.0 5.5 0.8 4.0 1.0 91.1 8.3 1.6 7.2 1.2
Oregon 5.7 1.0 6.0 1.0 4.8 0.8 19.0 5.5 1.4 5.8 1.4
Pennsylvania 6.7 0.8 7.1 1.0 6.5 1.1 3.4 6.6 1.4 6.7 1.2
Rhode Island 6.4 1.0 6.0 0.8 5.6 1.1 14.9 7.4 1.4 5.6 1.2
South Carolina 8.1 1.0 7.1 1.0 6.5 1.2 24.8 8.4 1.8 7.7 1.4
South Dakota 6.1 0.8 5.7 0.8 3.4 0.9 79.4 6.6 1.2 5.6 0.8
Tennessee 7.7 1.2 7.2 1.2 7.2 1.1 6.4 7.6 2.0 7.9 1.4
Texas 7.1 0.8 6.2 0.8 4.7 1.1 50.7 7.0 1.2 7.2 1.0
Utah 4.3 0.8 5.4 1.2 3.9 1.0 10.3 4.3 1.4 4.2 1.2
Vermont 5.1 0.8 4.4 0.8 4.5 1.2 13.1 4.6 1.0 5.5 1.0
(continues)
62 diabetes mellitus

TABLE II: PREVALENCE OF ADULTS WHO REPORTED EVER HAVING BEEN TOLD BY A
HEALTH PROFESSIONAL THAT THEY HAD DIABETES, 1991, 2000, AND 2001, AND BY SEX, 2001—
UNITED STATES, BEHAVIORAL RISK FACTOR SURVEILLANCE SYSTEM (continued)

Both sexes (%) Men Women

2001 2000 1991 Difference (2001) (2001)

State or Territory % 95% CI* (±) % 95% CI (±) % 95% CI (±) 1991–2001 % 95% CI (±) % 95% CI (±)

Virginia 6.0 1.0 6.2 1.4 4.2 1.1 43.9 6.2 1.4 5.8 1.4
Washington 5.7 0.8 5.5 0.8 5.0 1.0 13.3 6.2 1.2 5.2 1.0
West Virginia 8.8 1.2 7.6 1.2 6.0 1.0 47.7 8.9 1.6 8.8 1.6
Wisconsin 5.6 0.8 6.1 1.0 4.9 1.2 15.0 5.9 1.4 5.3 1.2
Wyoming 4.5 0.8 5.0 1.0 – – – 4.1 1.2 4.8 1.0
Guam 9.5 2.5 – – – – – 9.9 3.9 9.1 3.1
Puerto Rico 9.8 1.2 8.5 1.0 – – – 9.1 1.8 10.5 1.6
Virgin Islands 7.2 1.2 – – – – – 4.3 1.6 9.5 2.0

Summary

Both sexes Men Women

2001 2000 1991 (2001) (2001)

No. of states/territories 54 52 48 54 54
Median 6.6 6.2 4.8 6.6 6.5
Range 4.0–9.8 3.8–8.5 2.9–7.2 4.0–10.5 3.7–10.5
Mean 6.6 6.1 4.9 6.6 6.5
* Confidence interval.
†Not available or sample size <50 .
Source: Centers for Disease Control and Prevention, “State-Specific Prevalence of Selected Chronic Disease Related Characteristics—Behavioral
Risk Factor Surveillance System, 2001,” Morbidity and Mortality Weekly Report 52, no. 55–8 (August 22, 2003): 39.

widely publicized 1 in 8 risk for breast cancer
among US women.”
Communication Is Critical Between
Patients with Diabetes and Their Doctors
It is very important that people who have diabetes
understand the basics about their illness as well as
what they need to do in order to manage it suc-
cessfully. In one study, reported in a 2003 issue of
the Archives of Internal Medicine, interactions were
observed between 38 doctors and 74 of their
English-speaking patients when the physicians
were explaining new concepts to their patients.
The researchers found that when patients under-
stood what their doctors were telling them, they
were more likely to have good glycemic control.
This is particularly important among patients who
may have a poor grasp of their illness and what
they need to do to control it. Of particular help is
when doctors assess the patients’ understanding
level. According to the researchers, doing so can
“can uncover health beliefs, reinforce and tailor
health messages, and activate patients by opening a
dialogue.”
Poor Compliance with Treatment
The National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK) stated that study
results released in 2004 showed that less than 12
percent of people with diagnosed diabetes meet
their recommended treatment goals for blood glu-
cose, blood pressure, and cholesterol. This occurs
even though research has clearly shown that con-
trolling these conditions dramatically delays or pre-
vents diabetes complications.
Further, the percentage of people complying
with treatment recommendations has improved lit-
tle in the last decade. This is discouraging because
failure to control diabetes leads to an increased risk
for many complications, such as heart attack,
stroke, amputations, DIABETIC RETINOPATHY, DIABET-
IC NEUROPATHY, DIABETIC NEPHROPATHY, and death.
 diabetes mellitus 63

Complications from Diabetes age groups are either overweight or obese in com-
Although many people can control their diabetes parison to past years.
with diet, medication, exercise, and weight control,
an estimated 200,000 Americans die each year TABLE III: HOSPITAL DISCHARGE RATES FOR
from complications due to diabetes, making dia- DIABETES AMONG ADULTS 45 YEARS OF AGE
AND OLDER BY AGE, DISCHARGES PER 10,000
betes the sixth leading cause of death in the United POPULATION: UNITED STATES: 1990–2001
States. The key cause of diabetes-related complica-
tions is heart disease. Patients with diabetes have a Year 45–54 55–64 65–74 75 years+
two to four times greater risk of dying from heart 1990–1991 121.0 270.3 487.3 648.0
disease than patients who do not have diabetes. In 1992–1993 139.4 302.9 536.9 699.5
addition, patients with diabetes have a two to four 1994–1995 140.3 307.3 561.6 746.6
1996–1997 148.5 322.1 576.1 791.1
times greater risk of suffering from a stroke than 1998–1999 151.1 347.8 628.0 831.3
nondiabetic patients. In addition, 73 percent of 2000–2001 156.6 344.0 632.4 830.6
adults with diabetes have high blood pressure or
Source: Centers for Disease Control and Prevention. Chartbook on
are taking medications for hypertension. Trends in the Health of Americans. Health, United States, 2003.
Diabetes is also the leading cause of adult-onset
blindness. Between 12,000–24,000 people in the Costs of Diabetes
United States become blind each year as a result of
The federal government in the United States esti-
complications from diabetes. Others develop kid-
mates that the direct and indirect costs of diabetes
ney diseases; an estimated 38,000 people with dia-
are about $130 billion per year and the average
betes die from kidney failure each year in the
health care cost for a person with diabetes is about
United States.
five times greater than that of an age-matched per-
Diabetes is the leading cause of nontraumatic
son without diabetes. Some experts believe that
amputation in the United States. Many patients
these figures are underestimated.
with diabetes suffer amputations of the toes, feet,
and legs. An estimated 82,000 Americans have
Medications for Diabetes
body parts amputated each year as a result of dia-
betic complications. People with diabetes are also The medications used to treat diabetes mellitus
more likely to die from complications of flu or depend on whether the patient has Type 1 diabetes,
pneumonia, and from 10,000–30,000 people with which invariably requires some form of insulin deliv-
diabetes die of flu or pneumonia each year. Only ery, or Type 2 diabetes, which can often be treated
with oral medications. The Diabetes Prevention
slightly more than half of them (55 percent) get an
Program studied more than 3,000 people at risk for
annual flu shot although nearly all are eligible for
developing Type 2 diabetes (they had impaired glu-
such injections.
cose tolerance/prediabetes). Researchers compared
Increasing numbers of people with diabetes are
the effects of diet and exercise to treatment with
being hospitalized. For example, according to the
medication. One group was given medication
National Center for Health Statistics, in the years
(metformin), and individuals in a second group
1990–91, there were 121.0 hospital discharges per (the lifestyle group) were given information and
10,000 people among those individuals ages 45–54 the goal of dropping their body weight by 7 percent
years old. This rate has steadily increased. Over the by exercising. A third group was a placebo group.
period 2000–01, it was 156.6 per 10,000 people. The study was ended about a year earlier than
The rates of hospitalization also increased for indi- planned because the benefits of weight loss and
viduals in the age brackets of 55–64 years, 65–74 medication were so clear. The lifestyle group had a
years, and 75 years and older (see Table III). 58 percent lower incidence rate of diabetes than
Clearly, diabetes is becoming a greater problem for the placebo group. The medication group had a 31
middle-aged and senior adults than in past years, percent reduced occurrence of developing Type 2
possibly because so many more individuals in these diabetes compared with the placebo group. Clearly,
64 diabetic ketoacidosis
exercise and medication can prevent or delay Type
2 diabetes in many people.
Among those who are already diagnosed with
diabetes, studies have shown that improving
glycemic control to reduce hemoglobin A1c blood
tests by even 1 percent will reduce the risk of dia-
betic complications by 40 percent.
Prevention of Diabetes and Diabetic Complications
To date, Type 1 diabetes is a disease that is difficult
or even impossible to prevent, although it can be
well controlled with a careful diet, exercise, and
insulin therapy. Ongoing clinical studies are look-
ing at various means to delay or prevent the onset
of Type 1 diabetes in susceptible individuals, such
as those with impaired glucose tolerance.
Studies have indicated that Type 2 diabetes can be
prevented or delayed in patients at high risk. These
high-risk individuals are obese, have impaired glu-
cose tolerance and are considered to have predia-
betes, and are people with first-degree relatives
(such as a parent or sibling) with Type 2 diabetes.
See also DIABETIC KETOACIDOSIS; GESTATIONAL
DIABETES; HYPERGLYCEMIA; HYPOGLYCEMIA; IMPAIRED
GLUCOSE TOLERANCE; TYPE 1 DIABETES; TYPE 2 DIA-
BETES.
For further information, contact the following
organizations:
American Diabetes Association (ADA)
1701 North Beauregard Street
Alexandria, VA 22311
(703) 549-1500 or (800) 342-2383 (toll-free)
http://www.diabetes.org
National Diabetes Information Clearinghouse
1 Information Way
Bethesda, MD 20892
(800) 860-8747 (toll-free)
http://diabetes.niddk.nih.gov
American Diabetes Association. “Economic Costs of
Diabetes in the U.S. in 2002.” Diabetes Care 26, no. 3
(March 2003): 917–932.
Bardsley, Joan K., and Maureen Passaro, M.D. “ABCs of
Diabetes Research.” Clinical Diabetes 20, no. 1 (2002):
5–8.
Centers for Disease Control and Prevention, Chronic
Disease Prevention. “The Promise of Prevention:
Reducing the Health and Economic Burden of
Chronic Disease.” Department of Health and Human
Services, 2003.
Cherry, Daniel K., Catharine W. Burt, and David A.
Woodwell. “National Ambulatory Medical Care
Survey: 2001 Summary.” Division of Health Care
Statistics, Centers for Disease Control and Prevention,
no. 337, August 11, 2003.
Narayan, K. M., M.D., et al., “Lifetime Risk for Diabetes
Mellitus in the United States,” Journal of the American
Medical Association 290, no. 14 (October 8, 2003):
1884–1890.
National Institute of Diabetes and Digestive and Kidney
Diseases. “Most People with Diabetes Do Not Meet
Treatment Goals.” Press Release, National Institutes of
Health, January 20, 2004.
Petit, William A. Jr., M.D., and Christine Adamec. The
Encyclopedia of Diabetes. New York: Facts On File, Inc.,
2002.
Schillinger, Dean, M.D., et al. “Closing the Loop:
Physicians Communication with Diabetic Patients
Who Have Low Health Literacy.” Archives of Internal
Medicine 163, no. 1 (January 13, 2004): 83–90.
Tuomilehto, Jaako, M.D., et al. “Prevention of Type 2
Diabetes Mellitus by Changes in Lifestyle Among
Subjects with Impaired Glucose Tolerance.” New
England Journal of Medicine 344, no. 18 (May 3, 2001):
1,343–1,350.
diabetic ketoacidosis (DKA) An acute and often
severe metabolic complication that occurs to some
patients with diabetes (both TYPE 1 DIABETES and
TYPE 2 DIABETES). DKA involves a combination of
HYPERGLYCEMIA (excess acid in the blood) and DEHY-
DRATION.
DKA is so serious that it requires patients to be
hospitalized (usually in the intensive care unit) until
they are stabilized. In the worst cases, DKA may lead
to coma and death. Experts report a death rate of
5–10 percent among patients who lapse into diabet-
ic ketoacidosis. DKA may also cause cerebral (brain)
edema, which greatly heightens the risk of death,
especially among children with Type 1 diabetes.
Risk Factors for Developing DKA
The presence of diabetes is the major risk factor for
the development of DKA. Poor glycemic control

(patients’ inadequate monitoring of blood glucose
levels, poor nutrition, and inadequate therapy) is
another risk factor. However, sometimes blood lev-
els can change precipitously no matter how consci-
entious patients are about checking their blood.
One major problem is that not everyone who
has diabetes mellitus is actually aware that they
have the disease. In fact, they may first discover
their illness when they are hospitalized and diag-
nosed with DKA. Ethnicity is another key factor in
DKA. African Americans are twice as likely to be
admitted to the hospital for DKA as Caucasians.
Age is another risk factor, as DKA risks increase
with age.
Symptoms of DKA
Blurred vision, nausea, abdominal pains, and lack
of appetite are all common symptoms of DKA. The
individual may also experience increased urination
and great thirst. Dehydration may be both a symp-
tom and a cause of DKA.
Diagnosis and Treatment
The diagnosis of DKA is based on the patient’s clin-
ical presentation as well as on the results of tests,
such as blood glucose levels and urine and/or
serum acetone levels, all typically high in patients
with DKA. In addition, often an arterial blood gas
is drawn to measure the pH level in the blood,
which shows the level of acidity or alkalinity.
Normal pH is 7.4, while in patients with DKA, it is
less than 7.3.
Once DKA is diagnosed, the patient is given
aggressive fluid resuscitation as well as insulin.
Typically, short-acting insulin is administered intra-
venously and is followed by a continuous intra-
venous drip of the same insulin at a lower level. The
fluid that is usually given initially is normal saline.
Once the patient is producing urine, potassium gen-
erally needs to be administered as the vast majority
of patients with DKA have a total body deficit of
potassium. Once the emergency issues are treated,
the physician must determine the underlying cause
of the DKA and treat that cause aggressively.
Once the patient has sufficiently recovered, the
physician will emphasize the importance of main-
taining blood glucose levels that are as close to nor-
mal as possible with the hope that there will be no
diabetic nephropathy 65
further relapses into DKA. Patients who have been
hospitalized for DKA should wear a medical identi-
fication bracelet that shows they have diabetes so
that if the condition recurs, they will be likely to
obtain proper medical care in a timely manner. For
patients with diabetes, speed in treatment may
mean the difference between life and death.
See also COMA.
Glaser, Nicole, M.D., et al. “Risk Factors for Cerebral
Edema in Children with Diabetic Ketoacidosis.” New
England Journal of Medicine 344, no. 4 (January 25,
2001): 264–269.
Rewers, Arleta, M.D. “Predictors of Acute Complications
in Children with Type 1 Diabetes.” Journal of the
American Medical Association 287, no. 19 (May 15, 2002):
2,511–2,518.
diabetic nephropathy Kidney disease that stems
directly from DIABETES MELLITUS and that may ulti-
mately result in kidney failure. According to the
National Diabetes Information Clearinghouse, in
2001 nearly 43,000 patients with diabetes began
treatment for end-stage renal disease (another
name for kidney failure).
Patients who have diabetic nephropathy repre-
sent nearly half (42 percent) of all the kidney fail-
ure patients in the United States. Diabetic
nephropathy is also the cause for either kidney
dialysis or a kidney transplant among an estimated
100,000 people each year. Most patients with dia-
betic nephropathy also suffer from DIABETIC
RETINOPATHY, a disease of the eye.
Unfortunately, patients with kidney disease usu-
ally do not have any symptoms until less than 25
percent of their kidney function remains. However,
diligent testing by physicians, such as testing for
very small amounts of protein in the patient’s
urine, can often detect an early onset of kidney
dysfunction. Blood tests to measure creatinine and
blood urea nitrogen (BUN) can also be monitored
by physicians every three to six months, but these
tests are less sensitive than monitoring the urine
for protein. Increases in creatinine and BUN levels
are also indicators of kidney disease.
The current standard of care is to monitor the
patient first with a simple dipstick urine test. If pro-
66 diabetic nephropathy
tein is present in the urine, the patient has overt
proteinuria. The patient will need strict attention to
glycemic control, blood pressure, and lipids as well
as treatment with angiotensin-converting enzyme
(ACE) inhibitor mediations or angiotensin receptor
blockers (ARBs).
If no protein is seen in the urine dipstick test, a
second, more sensitive test for urine microalbu-
minuria can be obtained. Typically, this is a
radioimmunoassay that detects tiny amounts of
protein in the urine. If patients have less than 30
mcg of albumin per mg of creatinine, their levels
are considered normal. If the level is 30–300 mcg
albumin per mg of creatinine, patients have
microalbuminuria. These patients are treated with
ACE and/or ARB drugs, and strict attention is paid
to their glucose and lipid levels.
When the level is greater than 300 mcg of albu-
min per mg of creatinine, patients have macroal-
buminuria or overt proteinuria. Once a patient has
a serum creatinine level greater than 1.8 mg/dl or
has had greater than 1,000 mg of protein in their
urine over 24 hours, he or she should be referred to
a nephrologist for further consultation and therapy.
Causes of Nephropathy
The cause of diabetic nephropathy is often a com-
bination of both hypertension and diabetes.
Patients with these two medical problems have a
mortality risk that is increased by 37 times over
that of patients with one of these ailments. Patients
with diabetes who do not have hypertension can
also develop diabetic nephropathy, although their
risk is reduced compared with patients who have
both medical problems.
Because of the links connecting diabetes and
hypertension with kidney disease, patients with
both hypertension and diabetes must comply close-
ly with the medical regimens prescribed by their
physicians for decreasing high blood pressure.
These regimens include taking medication, losing
weight (if weight loss is recommended), and fol-
lowing other medical advice.
Patients with diabetes should work hard to keep
their glucose levels as close to normal as possible by
testing their blood on a regular basis and, if neces-
sary, acting on the information provided by the
blood tests. In a major study of people with dia-
betes, the federally funded Diabetes Control and
Complications Trial Research Group, 1,441 subjects
with Type 1 diabetes were studied from 1983–93.
The study definitively proved that the group that
successfully and tightly controlled their diabetes had
a 50 percent reduced risk for kidney disease (and
also a 60 percent reduced risk for nerve disease).
Signs and Symptoms
In the early stages of the disease, there may be few
or no symptoms, although there may be micro-
scopic levels of albumin and increased creatinine
levels. As the illness progresses the albumin and
creatinine levels increase, and the proteinuria
becomes apparent. If the patient’s kidneys further
deteriorate, symptoms such as malaise and itchy
skin may develop. Patients may show fatigue and
decreased endurance. They may also retain fluid in
the ankles and elsewhere in the body.
Physicians should check the urine of their
patients with diabetes on a regular basis to detect
any early signs of diabetic nephropathy. That way,
it can be treated before the condition becomes too
advanced and the patient requires kidney dialysis
and a kidney transplant.
Genetic Risks
Researchers have found that the siblings of patients
who have both diabetes and kidney disease have
five times the risk of developing diabetic nephropa-
thy themselves. In the future, doctors may be able
to estimate a patient’s risk by the detection of vari-
ous forms of the ACE gene.
Diagnosis and Treatment
The diagnosis of diabetic nephropathy is based on the
patient’s symptoms and laboratory tests. Physicians
may order a 24-hour urine collection, a test that pro-
vides a good estimate of kidney function and also
measures excess amounts of protein being lost in the
urine. If detected early, diabetic nephropathy can be
treated with medications. In most cases, ACE
inhibitors and/or ARB blockers are used to slow
down the progression of kidney disease.
Blood pressure is also a consideration. The goal
blood pressure may be as low as 120/70 if clinical-
ly indicated in patients with kidney disease.

See also BLOOD PRESSURE/HYPERTENSION; TYPE 1
DIABETES; TYPE 2 DIABETES.
Petit, William A. Jr., M.D., and Christine Adamec. The
Encyclopedia of Diabetes. New York: Facts On File, Inc.,
2002.
diabetic neuropathy Nerve damage directly
caused by diabetes. Diabetic neuropathy may result
in a variety of ailments, including a loss of feeling
in the feet or hands, the delayed digestion of food,
ERECTILE DYSFUNCTION, and many other medical
problems. About 60–70 percent of all patients with
diabetes will eventually suffer from some neuropa-
thy, ranging from a mild to a severe form.
Maintaining excellent glucose control may delay or
prevent the development of neuropathy.
When the nerves of the face are affected, dia-
betic neuropathy can mimic symptoms of a stroke
and may also cause a facial droop similar to that
found in Bell’s palsy. Diabetic neuropathy may also
cause an eyelid droop. These types of neuropathies
are caused by nerve attacks, a sudden blockage of
blood flow to the nerve. This problem is similar to
that of a heart attack or a stroke. Syndromes affect-
ing the cranial nerves are called cranial mononeu-
ropathies.
A radiculopathy is a painful neuropathy in
which a nerve root is directly affected. If the nerve
root supplying the area is located just below the
right lower ribs of the patient, it can mimic a gall-
bladder attack. If the radiculopathy is located in the
nerves of the lower legs, it can cause sciatica.
Other Focal Neuropathies
Patients with diabetes are more commonly affected
than nondiabetics by carpal tunnel syndrome (in
the fingers) and tarsal tunnel syndrome (in the
foot, typically in the heel). These syndromes may
occur because of a deposit of carbohydrates and
proteinlike material in the canals where the nerves
run. The problem may also be caused by medica-
tions as well as by blood flow problems.
Damage to the peroneal nerve in the foot can
lead to foot drop. This is the inability to extend the
foot, causing it to drag when walking.
diabetic neuropathy 67
Diagnosis
Physicians diagnose diabetic neuropathy based on
the patient’s medical history and physical examina-
tion. The most common form of neuropathy, the
stocking-glove form, or peripheral sensory neu-
ropathy, is often diagnosed based on history alone.
These patients typically complain of numbness, tin-
gling, burning, or a sense that something is in their
shoe. In addition, they note that their symptoms
increase when they remove their socks and shoes
and try to go to sleep. They often complain that the
bedclothes bother their feet. This very sensitive
feeling is called hyperesthesia.
Early on in this disorder, the nerve conduction
studies and electromyograms that are usually done
are not helpful and often have normal findings.
This is because they measure larger myelinated
nerve fibers that are affected much later in the
course of the disease. On examination, these
patients may have loss of ankle reflexes or changes
in sensory testing to stimuli such as vibration and a
light touch with nylon microfilaments.
Treatment
Diabetic neuropathy may also cause chronic and
sometimes severe pain. People with diabetes may
need medications or creams. The first therapy is to
tighten glucose control to as near-normal levels as
possible. Patients are also counseled to stop smok-
ing and to normalize their blood pressure and lipid
levels. Often medications are given at bedtime,
when patients’ symptoms are typically the worst.
Simple analgesics such as acetaminophen
(Tylenol) may be given to patients. The drug tra-
madol (Ultram), which is a nonnarcotic and not a
nonsteroidal anti-inflammatory medication (NSAID),
is given if acetaminophen provides insufficient pain
relief. Many people do not wish to take narcotics or
NSAIDs because of their side effects. The next med-
ication usually tried is in the class of antiseizure or
antidepressant medications. Antidepressants such as
amitriptyline (Elavil) or nortriptyline (Aventyl or
Pamelor) or the antiseizure drug gabapentin
(Neurontin) may be used.
When a patient has a lancinating (shooting) form
of pain, carbamazepine (Tegretol) is also very helpful.
Memantine (Namenda and Axura), a medication
68 diabetic retinopathy
currently indicated to treat Alzheimer’s disease, has
also been found to be effective in reducing neuro-
pathic pain for patients.
If the neuropathy is in a very localized area, top-
ical medications such as capsaicin or lidocaine can
be used. As a last resort, narcotics have been used
with success.
See also TYPE 1 DIABETES; TYPE 2 DIABETES.
The Diabetes Control and Complications Trial Research
Group. “The Effect of Intensive Diabetes Therapy on
the Development and Progression of Neuropathy.”
Annals of Internal Medicine 122, no. 8 (April 15, 1995):
561–568.
Petit, William A. Jr., M.D., and Christine Adamec. The
Encyclopedia of Diabetes. New York: Facts On File, Inc.,
2002.
diabetic retinopathy Disease of the retina of the
eye, directly stemming from diabetes mellitus.
Diabetic retinopathy is the most common eye dis-
ease found among people diagnosed with diabetes.
According to the National Institutes of Health
(NIH), diabetic retinopathy causes from
12,000–24,000 new cases of blindness each year
and is estimated to cause 12 percent of all new
cases of blindness each year. It is also the leading
cause of adult-onset blindness.
Diabetic retinopathy is at least partially caused by
high levels of glucose that result in varying levels of
harm to the blood vessels in the retina. Other fac-
tors, such as a genetic predisposition to developing
the disease, hypertension, smoking, hyperlipidemia,
and kidney disease, may worsen the retinopathy.
An early diagnosis, determined by a dilated eye
examination and followed by appropriate treat-
ment, could prevent the loss of sight for over 90
percent of patients with diabetes. Because the early
stages of the disease produce no symptoms, only an
early eye examination will detect possible prob-
lems. However, according to the National Institutes
of Health, less than half (47 percent) of all patients
diagnosed with diabetes have annual eye examina-
tions. In its Healthy People 2010 plan, the federal
government has set a goal that 75 percent of all
adults with diabetes have a dilated eye examina-
tion each year.
The National Diabetes Eye Examination Program
offers free eye examinations to patients with dia-
betes who are over age 65 and on Medicare.
Risk Factors
People with TYPE 1 DIABETES are at greater risk for
developing retinopathy than patients with TYPE 2
DIABETES. In fact, almost all patients who have had
Type 1 diabetes for 15 or more years have some
degree of retinopathy. Patients with Type 2 diabetes
who require insulin are also likely to develop
retinopathy.
African Americans who have Type 1 diabetes are
particularly at risk for developing diabetic retinopa-
thy. In fact, African Americans with diabetes face a
40–50 percent greater risk than Caucasians with dia-
betes of developing diabetic retinopathy. Hispanics
with diabetes, especially Mexican Americans, are also
at high risk for developing the condition. It is also
possible for children who have diabetes to suffer
from diabetic retinopathy, although the risk appears
to be low, especially prior to the onset of puberty.
The people with diabetes who are the most like-
ly to suffer from diabetic retinopathy include those
who:
• Did not control their diabetes in the first years
after diagnosis
• Have had diabetes for 17 or more years
• Experience high blood pressure
• Are African American, Native American, or
Hispanic
• Have high cholesterol levels
• Have had gestational diabetes
• Are smokers
• Abuse alcohol
• Have other illnesses, such as kidney disease
• Have a genetic risk for eye disease
Indications of Diabetic Retinopathy
Few symptoms of early diabetic retinopathy are
detectable to the patient. This is why screening
examinations are so critical. Some early symptoms
may be a worsening of peripheral (side) vision or
worse color vision. A dilated eye examination per-